Field of the Invention
The present disclosure relates generally to medical treatments and more specifically to a method and device for treating arrhythmias of the heart, such as tachycardia and cardiac fibrillation.
Background Information
Arrhythmia is a variation from the normal rhythm of the heart beat. Cardiac arrhythmias are an important cause of morbidity and mortality. The major cause of fatalities due to cardiac arrhythmias is the subtype of ventricular arrhythmias known as ventricular fibrillation (VF). Conduction of electrical impulse is a unique property of cardiac and skeletal muscle and nervous tissue and is fundamental to their physiologic function. Abnormal cardiac electrical impulse generation and propagation underlies the pathogenesis of several diseases, including ventricular fibrillation (see, Santinelli et al., Int J Cardiol., 3(1):109-111 (1983); Kanani et al., J Cardiovasc Pharmacol. 32(1):42-48 (1998); and Amitzur et al., Cardiovasc Drugs Ther., 17(3):237-247 (2003)), a leading cause of death in the developed world.
To stop VF in an attempt to return the heart to a normal rhythm, automatic external defibrillators (AED) are widely in use in healthcare and non-healthcare settings. In addition, implantable defibrillators are highly useful in management of a number of chronic heart conditions. For example, Sudden Cardiac Death (SCD), which is often due to ventricular fibrillation, accounts for over 400,000 deaths annually in the United States. Several clinical trials have shown survival benefit in SCD survivors who receive implantable defibrillators. Recent trials have also shown that patients who are at risk for SCD also benefit from this therapy and implantable defibrillators have been used in this population with significant reduction in mortality.
The physical structure of defibrillator systems can be generally illustrated with reference to the implantable format. Such defibrillator systems contain a hermetically sealed “Can” that houses the battery, electronic circuitry and capacitors. These devices are implanted in the chest wall and electrodes are deployed intravascularly to stimulate, pace and deliver high energy defibrillatory shocks to defibrillate the heart. The electrode/lead is typically placed through the subclavian vein into the endocardium.
Three modes of therapies are used by the implantable defibrillators to treat dangerous arrythmias: 1) anti-tachycardia pacing; 2) low energy cardioversion; and 3) high energy defibrillation. Among the three, only high energy defibrillaton has been shown to be effective in defibrillating the heart during ventricular fibrillation.
Several different electrode configurations have been used to deliver the high energy including, epicardial lead systems (U.S. Pat. Nos. 5,342,407 and 5,603,732), endocardial lead systems, and subcutaneous electrodes (U.S. Pat. Nos. 5,133,353, 5,261,400, and 5,620,477). The housing of the defibrillator can also serve as an additional electrode during delivery of defibrillatory shocks and for pacing (U.S. Pat. No. 5,658,321). Recently, a totally subcutaneous-non-vascular system that is capable of delivering pacing and high voltage defibrillatory shocks has also been described (U.S. Pat. No. 7,536,222).
Currently the principal approach to terminating fibrillation using implantable or external systems is by delivering a high voltage DC shock to cause defibrillation of the heart. This is achieved by charging a capacitor and delivering the charge to the heart over a period of typically 4-16 msec. As such, the current defibrillator circuitry includes high performance capacitors capable of rapidly charging and discharging charge, causing a brief period of high current density in the myocardium that causes defibrillation. There may be multiple capacitors controlled by a circuit and typically 5-40 Joules of energy are delivered to achieve defibrillation.
While effective in many cases, existing defibrillation systems have drawbacks. For example, the energy delivered may be insufficient in magnitude or timing of delivery to stop fibrillation. Low frequency DC and AC are known to be pro-fibrilliatory. In addition, the large electric field applied in defibrillation also leads to significant skeletal muscle stimulation which has been implicated in the pain that follows defibrillation shocks.
Further, the current methodology used to treat cardiac arrhythmias using DC fields is associated with a host of adverse effects that include cellular injury by way of electroporation (see, Tung, Methods Mol Biol., 48:253-271 (1995); Tung et al., Ann N Y Acad Sci., 720:160-175 (1994); and Al-Khadra et al., Circ Res., 87(9):797-804 (2000)), cardiac conduction disturbances (see, Kanani et al., J Cardiovasc Pharmacol., 32(1):42-48 (1998); and Eysmann et al. Circulation., 73(1):73-81 (1986)), mechanical dysfunction (see, Tung et al., Ann N Y Acad Sci., 720:160-175 (1994); Mollerus et al., J Interv Card Electrophysiol., 19(3):213-216 (2007); and Tokano et al., J Cardiovasc Electrophysiol., 9(8):791-797 (1998)), and increased mortality due to heart failure (see, Moss et al., N Engl J Med., 346(12):877-883 (2002); and Bardy et al., N Engl J Med., 352(3):225-237 (2005)).
The present invention is based on the discovery of the previously unrecognized biophysical phenomenon of reversible cardiac conduction block using sustained AC fields that is without residual electrophysiological consequence and can be applied with less perceived pain than existing defibrillatory methods. Cardiac cells remain in a refractory state for the duration of field stimulation by elevation of Vm, a phenomenon that is distinctly different from the effect of DC fields. Further, the cell response to sustained AC fields appears to be devoid of the deleterious effects commonly observed during DC field stimulation. Hence, cardiac conduction block using AC may provide a safer alternative for terminating cardiac arrhythmias.
Low frequency AC (50-60 Hz) waveforms were the first form of electrical therapy used to treat VF, but was abandoned because of its high risk of proarrhythmia (see, Gurvich et al., Am Rev Soy Med., 4(3):252-256 (1947); Smith et al., Am J Pathol., 47:1-17 (1965); and Lown et al. Am J Cardiol., 10:223-233 (1962). Indeed, 50 Hz AC has successfully found its way into the current generation implantable defibrillators as an efficient way to induce VF (see, Malkin et al., Med Biol Eng Comput., 41(6):640-645 (2003); and Mower et al. Circulation., 67(1):69-72 (1983)).
However, few studies have evaluated the effects of higher AC frequencies in intact hearts. Previous studies used AC in intact guinea pig hearts and demonstrated a frequency-dependent increase in pacing threshold (see, Weirich et al. Basic Res Cardiol., 78(6):604-616 (1983)) and fibrillation threshold (see, Weirich et al. Basic Res Cardiol., 78(6):604-616 (1983); and Geddes et al., Med Biol Eng., 7(3):289-296 (1969)) for frequencies up to the kilohertz range.
Roberts et al. evaluated the defibrillation efficacy of AC frequencies up to 1 kHz, but with a maximum duration of 32 cycles (Pacing Clin Electrophysiol., 26(2 Pt 1):599-604 (2003). They concluded that a 200 Hz, 2 cycle waveform was most effective to achieve external defibrillation.
Sweeney et al. used monophasic rectangular pulses for open chest defibrillation in dogs and showed that the energy and current requirement was significantly higher at frequencies>1 kHz (J Cardiovasc Electrophysiol., 7(2):134-143 (1996).
All the above studies relied on defibrillation by the onset of the electric field, and none of the studies explored longer duration field pulses to block conduction as a way to prevent re-initiation of VF. Although conduction block might be expected in the range of frequencies tested in these previous studies, this biophysical phenomenon was not specifically explored. More importantly, the short duration of the high frequency AC field (2-32 cycles) might not have been sufficient to extinguish multiple reentrant wave fronts present in VF.
However, the cellular electrophysiological effects of sinusoidal AC field stimulation have not been systematically studied in cardiac tissue. Meunier et al. demonstrated prolongation of action potential duration in cardiac tissue subject to low frequency (50 Hz) sinusoidal AC stimulation (J Cardiovasc Electrophysiol., 12(10):1176-1184 (2001); and J Cardiovasc Electrophysiol., 10(12):1619-1630 (1999)). The plateau of the action potential remained elevated, and the amplitude of Vm oscillation was inversely related to the frequency of AC field up to 100 Hz, the maximum frequency used in their study.
Frequency dependent conduction block in excitable tissue such as the neural axons and peripheral nerves have been demonstrated (see, Tanner, Nature, 195:712-713 (1962); and Woo et al., Bulletin Los Angeles Neurological Society, 29:87-94 (1964)). Kilgore et al. reported high frequency nerve conduction block in the peripheral nerve using 3-5 kHz biphasic current (Kilgore et al., Med. Biol. Eng. Comput., 42:394-406 (2004)). Animal experiments have also shown that high-frequency alternating electrical current applied to peripheral nerves can block conduction of action potentials (see, Tanner, Nature, 195:712-713 (1962); Reboul et al., Am. J. Physiol., 125:205-215 (1939); Rosenblueth et al., Am. J. Physiol., 125:251-264 (1939); and Bowman et al., Appl. Neurophysiol., 49:121-138 (1986)). This nerve block was quickly reversible once the stimulation was removed suggesting that this was not due to repeated stimulation resulting in fatigue (see, Kilgore et al., Med. Biol. Eng. Comput., 42:394-406 (2004)). Subsequently, others have reported similar findings in a lumped circuit model of the myelinated axon based on Frankenhaeuser-Huxley model. The mode of conduction block was demonstrated to be due to constant activation of potassium channels, thus antagonizing sodium channel induced depolarization (see, Zhang et al., IEEE Trans. Biomed. Eng., 53:2445-54 (2006)). To date, however, such methods are not being applied to the heart; e.g., to minimize pain associated with the delivery of a defibrillating current.
Further, use of radio frequency (RF) energy has been used to produce temporary conduction block in local areas of a heart. U.S. Pat. No. 6,431,173 describes a method of using electrical energy to produce temporary conduction block in a local region of the patient's myocardium to disrupt a reentry pathway through which an atrial or ventricular tachycardia (or other type of arrhythmia) is initiated and perpetuated, thereby resulting in cardioversion or defibrillation. However, use of RF to for terminating tachyarrhythmias may cause permanent myocardial damage.
Based on the current state of treatment of arrhythmias, there is a need for an improved device and method to terminate cardiac fibrillation to provide less painful treatment of arrhythmias.